The renin-angiotensin system is involved in the homeostasis to control systemic blood pressure, body fluid amount, balance among the electrolytes, etc. together with aldosterone system. The relation between renin-angiotensin and hypertension has been clarified based on the fact that angiotensin II having potent vasoconstrictive action elevates blood pressure via the angiotensin II receptors on the cellular membrane, and therefore, the antagonist of angiotensin II has been used for the treatment of hypertension caused by angiotensin. So far, drugs having angiotensin II antagonistic activity have been clinically applied by oral administration, however, said drugs are applied for symptomatic therapy which needs long term repeated administration. Therefore, due to the necessity for continuous administration, simultaneous administration with other drugs for oral administration, etc., the burden on the patient receiving oral administration of this kind of drug can not be ignored.
Moreover, there is a possibility that condition of the patient changes due to interruption of taking this kind of drug, etc. Thus, oral administration of drugs having angiotensin II antagonistic activity is not necessarily satisfactory in view of safe and reliable treatment.
In Pharmaceutical Research, 14, 887-891 (1997), there is reported a sustained-release preparation for 2-ethyl-5,7-dimethyl-3-[[2′-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]imidazo[4,5-b]pyridine having angiotensin II antagonistic activity, said preparation containing high molecular (Mw 82,000) polylactide and polyethylene-glycol 400 distearate and it is described that initial burst from the sustained-release preparation, whose drug content is about 10%, is about 20%.
In the Japanese publication translation of International patent application No. 504017/1998, a composition characterized in that a physiologically active protein together with a metal cation component is dispersed in a biocompatible polymer is disclosed.